Dr Perdomo's interests include elucidation of the mechanisms that lead to immune thrombocytopenia (low platelet counts) (ITP) and drug-induced thrombocytopenia (DITP). Low platelet numbers can result in internal bleeding and even death. Several prescription drugs produce immune reactions that lead to the production of drug-dependent antibodies that cause platelet damage. Similar antibodies that cause low platelet counts are produced in autoimmune conditions such as ITP. His research has found that these auto-antibodies do not only damage circulating platelets but also their cellular precursors (called megakaryocytes). Affected megakaryocytes show diminished platelet production capacity.

He is currently investigating the cellular and molecular mechanisms by which antibodies cause megakaryocyte impairment using a humanized mouse model. This research will lead to a more complete understanding of the pathogenesis of immune thrombocytopenia and may contribute to the implementation of improved treatments options.

Another important area of research is heparin-induced thrombocytopenia and thrombosis (HIT). HIT is a serious antibody-mediated condition developed by many patients undergoing heparin treatment (eg, during surgery). HIT is characterised by low platelet numbers and clot formation. Clots can form anywhere. For instance, clotting in the legs produces gangrene, which often results in amputation. The death rate from HIT is still unacceptably high. Current therapies are limited and a therapy the stops HIT in affected patients is urgently needed.

An antibody fragment that counteracts the effect of the HIT antibodies has been designed and has been successfully tested in our laboratory. This antibody fragment is now undergoing tests in a mouse model of HIT, with promising results. The activity of this novel molecule will stop the action of the HIT antibody thus preventing the progression this condition.

Antibody engineering research has also led to the development of a bispecific molecule (a molecule with two distinct functions) that interacts with activated platelets (ie, those found at the sites of clotting) and inhibits platelet aggregation and clot formation. This bispecific molecule is active in mice and is being developed as an antithrombotic targeted drug.

Perdomo JS, 2000, 'Eos and Pegasus, Two Members of the Ikaros Family of Proteins with Distinct DNA Binding Activities', The Journal of Biological Chemistry, vol. 275, pp. 38347 - 38354, http://dx.doi.org/10.1074/jbc.M005457200